Why does depression surge so dramatically in adolescence, especially for females? Despite the great scientific and public health significance of this question, the mechanisms underlying the surge in depression and emergence of gender differences in depression during adolescence remain elusive. This application is relevant to NIMH's mission to understand the causes of depression in youth, role of minority and gender status in depression, and targets for early intervention. The aims of this application are to examine the generality to African-Americans of this surge in depression and emergence of gender differences as well as to examine the mechanisms underlying these developmental phenomena from the perspective of an innovative genetic-cognitive vulnerability X transactional stress model, embedded within a normative adolescent brain and cognitive development context. To this end, a large-scale prospective, longitudinal study of 600 12-year old community youth (evenly divided between males and females and Caucasians and African-Americans) and their parents will be conducted. Assessments of children's cognitive and genetic (serotonin transporter gene polymorphism;Year 2 only) vulnerability, normative cognitive development, racial identity, and psychiatric diagnoses will be conducted at Time 1 and yearly thereafter. Assessments of psychiatric symptoms, negative life events, hopelessness, emotional abuse and peer victimization, perceived discrimination, body image, and pubertal status will occur every 6 months. In addition, assessments of parental psychopathology and parental cognitive vulnerability will be obtained from Ps'mothers at Time 1. Finally, information about parenting styles and parental inferential feedback will be obtained from Ps'mothers at Time 1 and yearly. Results will have very significant implications for prevention of depression. Knowledge of mechanisms underlying the adolescent surge in depression would suggest interventions for short-circuiting it and the great impairment it portends for young adulthood. Specifically, results will suggest optimal features of preventive interventions for depression in youth regarding: identification of youth to target, timing, psychological or biological processes to target, and interventions for girls vs. boys and African-Americans vs. Caucasians. PUBLIC HEALTH RELEVANCE: This application is unique in that it will provide a major prospective study of the generality across ethnic groups of the adolescent surge in depression and emergence of gender differences and test mechanisms underlying these two developmental phenomena from the perspective of an integrated cognitive vulnerability-stress/genetic vulnerability- stress model. In addition, developmental trajectories of executive functions relevant to the genesis of cognitive vulnerability to depression, informed by knowledge of normative adolescent brain and cognitive development, will be examined. By isolating the risk factors and mechanisms underlying the development of depression in adolescence, the project's findings will have significant implications for the prevention of depression, particularly in the area of optimal timing and targeting (i.e., high cognitive and/or genetic risk) of interventions that could be tailored appropriately to address gender and ethnic differences.